Do older adults mistake the accelerator for the brake pedal?: Older adults employ greater prefrontal cortical activity during a bipedal/bimanual response-position selection task.

Successful aging depends upon maintaining executive functions, which enable flexible response coordination. Although flexible responses are required for both hands and feet, as in driving, few studies have examined executive functions and brain activity in older adults, in terms of foot responses. In this study, younger (mean age = 20.

Hodgkin Lymphoma: Biology and Differential Diagnostic Problem.

Hodgkin lymphomas (HLs) are lymphoid neoplasms that are morphologically defined as being composed of dysplastic cells, namely, Hodgkin and Reed-Sternberg cells, in a reactive inflammatory background. The biological nature of HLs has long been unclear; however, our understanding of HL-related genetics and tumor microenvironment interactions is rapidly expanding. For example, cell surface overexpression of programmed cell death 1 ligand 1 (CD274/PD-L1) is now considered a defining feature of an HL subset, and targeting such immune checkpoint molecules is a promising therapeutic option.

Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells.

Label-free image analysis has several advantages with respect to the development of drug screening platforms. However, the evaluation of drug-responsive cells based exclusively on morphological information is challenging, especially in cases of morphologically heterogeneous cells or a small subset of drug-responsive cells. We developed a novel label-free cell sub-population analysis method called "in silico FOCUS (in silico analysis of featured-objects concentrated by anomaly discrimination from unit space)" to enable robust phenotypic screening of morphologically heterogeneous spinal and bulbar muscular atrophy (SBMA) model cells.

Stochastic evaluation of four-component relativistic second-order many-body perturbation energies: A potentially quadratic-scaling correlation method.

A second-order many-body perturbation correction to the relativistic Dirac-Hartree-Fock energy is evaluated stochastically by integrating 13-dimensional products of four-component spinors and Coulomb potentials. The integration in the real space of electron coordinates is carried out by the Monte Carlo (MC) method with the Metropolis sampling, whereas the MC integration in the imaginary-time domain is performed by the inverse-cumulative distribution function method. The computational cost to reach a given relative statistical error for spatially compact but heavy molecules is observed to be no worse than cubic and possibly quadratic with the number of electrons or basis functions.

Live imaging-based assay for visualising species-specific interactions in gamete adhesion molecules.

Successful gamete fusion requires species-specific membrane adhesion. However, the interaction of adhesion molecules in gametes is difficult to study in real time through low-throughput microscopic observation. Therefore, we developed a live imaging-based adhesion molecule (LIAM) assay to study gamete adhesion molecule interactions in cultured cells.

A cryptic phosphate-binding pocket on the SPFH domain of human stomatin that regulates a novel fibril-like self-assembly.

Human stomatin (hSTOM) is a component of the membrane skeleton of erythrocytes that maintains the membrane's shape and stiffness through interconnecting spectrin and actin. hSTOM is a member of the protein family that possesses a single stomatin/prohibitin/flotillin/HflK (SPFH) domain at the center of the molecule. Although SPFH domain proteins are widely distributed from archaea to mammals, the detailed function of the domain remains unclear.

Evaluation of the Geenius HIV 1/2 confirmatory assay for HIV-2 samples isolated in Japan.

Background: Although the number of HIV-2-infected individuals is quite low in Japan, at least three groups of HIV-2 (A, B and CRF01_AB) have been detected thus far. In particular, CRF01_AB HIV-2 cases have been found only in limited areas, Cote d'Ivoire and Japan. Here, we demonstrate that Geenius HIV 1/2 Confirmatory Assay (Geenius, Bio-Rad Laboratories) is able to detect HIV-2 samples, including groups A, B and CRF01_AB, isolated in Japan.

Mutational Activation of the NRF2 Pathway Upregulates Kynureninase Resulting in Tumor Immunosuppression and Poor Outcome in Lung Adenocarcinoma.

Activation of the NRF2 pathway through gain-of-function mutations or loss-of-function of its suppressor KEAP1 is a frequent finding in lung cancer. NRF2 activation has been reported to alter the tumor microenvironment. Here, we demonstrated that NRF2 alters tryptophan metabolism through the kynurenine pathway that is associated with a tumor-promoting, immune suppressed microenvironment.

Complete Chemical Synthesis of Minimal Messenger RNA by Efficient Chemical Capping Reaction.

Site-specific chemical modification of mRNA can improve its translational efficiency and stability. For this purpose, it is desirable to develop a complete chemical synthesis method for chemically modified mRNA. The key is a chemical reaction that introduces a cap structure into the chemically synthesized RNA.

Green spotted puffers detect a nontoxic TTX analog odor using crypt olfactory sensory neurons.

Toxic puffers accumulate their defense substance (tetrodotoxin; TTX) through the food chain. Although the previous study suggests that 5,6,11-trideoxyTTX, a nontoxic TTX analog detected simultaneously with TTX in toxic puffers or their prey, acts as an olfactory chemoattractant for grass puffers, it is unclear whether toxic puffers are commonly attracted to 5,6,11-trideoxyTTX, and which types of olfactory sensory neurons (OSNs) detect 5,6,11-trideoxyTTX. Here, we demonstrated that green spotted puffer, a phylogenetically distant species from the grass puffer, is attracted to 5,6,11-trideoxyTTX.

Maternal embryonic leucine zipper kinase (MELK) optimally regulates the HIV-1 uncoating process.

Human immunodeficiency virus type-1 (HIV-1) attaches to target cells and releases the capsid, an essential component of the viral core that contains viral RNA, into the cytoplasm. After invading target cells, the core structure gradually collapses. The timing of the disassembly of the HIV-1 capsid is essential for efficient viral cDNA synthesis and transport into the nucleus.

Spindle motility skews division site determination during asymmetric cell division in Physcomitrella.

Asymmetric cell division (ACD) underlies the development of multicellular organisms. In animal ACD, the cell division site is determined by active spindle-positioning mechanisms. In contrast, it is considered that the division site in plants is determined prior to mitosis by the microtubule-actin belt known as the preprophase band (PPB) and that the localization of the mitotic spindle is typically static and does not govern the division plane.

Systemic Regulation of Iron Acquisition by Arabidopsis in Environments with Heterogeneous Iron Distributions.

Nutrient distribution within the soil is generally heterogeneous. Plants, therefore, have evolved sophisticated systemic processes enabling them to optimize their nutrient acquisition efficiency. By organ-to-organ communication in Arabidopsis thaliana, for instance, iron (Fe) starvation in one part of a root drives the upregulation of a high-affinity Fe-uptake system in other root regions surrounded by sufficient levels of Fe.

Quantification of cyanobacterial cyclic di-guanosine monophosphate (c-di-GMP) by liquid chromatography electrospray ionization tandem mass spectrometry.

Cyclic di-guanosine monophosphate (c-di-GMP) is a second messenger found ubiquitously in bacteria. This signaling molecule regulates a variety of physiological activities such as phototaxis and flocculation in cyanobacteria and is critical for their environmental adaptation. Although genes encoding the enzymes for synthesis and/or degradation of c-di-GMP are found in the genomes of both multicellular and unicellular cyanobacteria, little is known about the biological functions of these enzymes in cyanobacterial cells.

Administration of suppresses DSS-induced colitis.

, a filamentous fungus, has long been used for the production of traditional Japanese foods. Here, we analyzed how administration affects the intestinal environment in mice. The results of 16S rRNA gene sequencing of the gut microbiota indicated that after the administration of heat-killed spores, the relative abundance of an anti-inflammatory strain became 2.

Development of Fluorophosphoramidate as a Biocompatibly Transformable Functional Group and its Application as a Phosphate Prodrug for Nucleoside Analogs.

Synthetic phosphate-derived functional groups are important for controlling the function of bioactive molecules in vivo. Herein we describe the development of a new type of biocompatible phosphate analog, a fluorophosphoramidate (FPA) functional group that has characteristic P-F and P-N bonds. We found that FPA with a primary amino group was relatively unstable in aqueous solution and was converted to a monophosphate, while FPA with a secondary amino group was stable.

Parallelism Between Sentence Structure and Nominal Phrases in Japanese: Evidence from Scrambled Instrumental and Locative Adverbial Phrases.

The present study investigated the canonical position of instrumental and locative adverbial phrases in both Japanese sentences and noun phrases to determine whether the canonical positions are parallel. A series of sentence/phrase decision tasks were used to compare sentences with different word-orders, including sentences with SAdvOV (S is subject phrase, Adv adverb, O object phrase and V verb), AdvSOV, SAdvOV and SOAdvV word orders. SAdvOV word order was found to be the most quickly processed, for both instrumental adverbial (Experiment 1) and locative adverbial phrases (Experiment 2).

Distribution and Structure Analysis of Fibril-Forming Peptides Focusing on Concentration Dependency.

We focus on the concentration dependency of fibril-forming peptides, which have the potential of aggregation by themselves. In this study, we performed replica-exchange molecular dynamics simulations of Lys-Phe-Phe-Glu (KFFE) fragments, which are known to form fibrils in experiments under different concentration environments. The analysis by static structure factors suggested that the density fluctuation of the KFFE fragments becomes large as the concentration increases.

A hierarchical transcriptional network activates specific CDK inhibitors that regulate G2 to control cell size and number in Arabidopsis.

How cell size and number are determined during organ development remains a fundamental question in cell biology. Here, we identified a GRAS family transcription factor, called SCARECROW-LIKE28 (SCL28), with a critical role in determining cell size in Arabidopsis. SCL28 is part of a transcriptional regulatory network downstream of the central MYB3Rs that regulate G2 to M phase cell cycle transition.

Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis.

SignificanceScramblases translocate lipids across the lipid bilayer without consumption of ATP, thereby regulating lipid distributions in cellular membranes. Cytosol-to-lumen translocation across the endoplasmic reticulum (ER) membrane is a common process among lipid glycoconjugates involved in posttranslational protein modifications in eukaryotes. These translocations are thought to be mediated by specific ER-resident scramblases, but the identity of these proteins and the underlying molecular mechanisms have been elusive.

Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy.

The tumor suppressor protein p53, a transcription product of the anti-oncogene , is a critical factor in preventing cellular cancerization and killing cancer cells by inducing apoptosis. As a result, p53 is often referred to as the "guardian of the genome." Almost half of cancers possess genetic mutations in the gene, and most of these mutations result in the malfunction of p53, which promotes aggregation.

Signal Sequence-Dependent Orientation of Signal Peptide Fragments to Exosomes.

Signal peptides (SPs) not only mediate targeting to the endoplasmic reticulum (ER) but also play important roles as biomarkers and substances with physiological activity in extracellular fluids including blood. SPs are thought to be degraded intracellularly, making it unclear how they are transported from the ER to the extracellular fluid. In a recent study, we showed that a C-terminal fragment of the SP of a type I membrane protein, amyloid precursor protein (APP), was secreted into the extracellular fluid via exosomes using transformed HEK293 cells expressing APP SP flanking a reporter protein.